Hydrogen sulfide (H2S) has been recognized as an important biological molecule and plays important biological and pharmacological roles in different conditions associated with human health. For example, H2S has been implicated in hypertension, diabetes, diseases of mental deficiency, asthma, stroke, and other conditions. Slow releasing H2S donating molecules have been used both as research tools and in clinical trials to abate different disease states. For example, administration of H2S results in reduction in blood pressure in hypertensive mice. Additionally, the negative GI trauma that is caused by popular NSAIDs appears to be abated by sulfide-donating molecules during drug-delivery.
Although convenient, direct administration of H2S or sulfide-containing salts leads to a large burst of released H2S, which is quickly metabolized/oxidized by cellular components as part of a toxicological response, and merely results in a disruption of redox homeostasis rather than elevated H2S levels. Motivated by these limitations, researchers have developed “slow-releasing” H2S donors that deliver H2S at a sustained, slow rate, more consistent with enzymatic production. One major limitation of these donor constructs is that they do not allow for H2S to be triggered by a biological response. For example, H2S is well established to provide protection against oxidative stress damage, such as that incurred during myocardial infarction (MI) or ischemia reperfusion injury. There exists a need in the art for an H2S delivery platform that does not release H2S until challenged with reactive components.